rs468646

Positions:

• chr21-41437279-A-C
• chr21-41437279-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002462.5(MX1):​c.436+127A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 969,452 control chromosomes in the GnomAD database, including 96,358 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.37 (12139 hom., cov: 31)
  • Exomes 𝑓: 0.43 (84219 hom.)
• Consequence: MX1 NM_002462.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.776

Genes affected

MX1 (HGNC:7532): (MX dynamin like GTPase 1) This gene encodes a guanosine triphosphate (GTP)-metabolizing protein that participates in the cellular antiviral response. The encoded protein is induced by type I and type II interferons and antagonizes the replication process of several different RNA and DNA viruses. There is a related gene located adjacent to this gene on chromosome 21, and there are multiple pseudogenes located in a cluster on chromosome 4. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MX1	NM_002462.5	c.436+127A>C		intron_variant		ENST00000398598.8	NP_002453.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MX1	ENST00000398598.8	c.436+127A>C		intron_variant		1	NM_002462.5	ENSP00000381599	P1

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56557 AN: 151902 Hom.: 12142 Cov.: 31

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.308

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.00732

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.501

Gnomad OTH AF: 0.370

GnomAD4 exome AF: 0.430 AC: 351289 AN: 817432 Hom.: 84219 AF XY: 0.427 AC XY: 178305 AN XY: 418028

Gnomad4 AFR exome AF: 0.199

Gnomad4 AMR exome AF: 0.242

Gnomad4 ASJ exome AF: 0.316

Gnomad4 EAS exome AF: 0.00376

Gnomad4 SAS exome AF: 0.265

Gnomad4 FIN exome AF: 0.475

Gnomad4 NFE exome AF: 0.493

Gnomad4 OTH exome AF: 0.395

GnomAD4 genome AF: 0.372 AC: 56573 AN: 152020 Hom.: 12139 Cov.: 31 AF XY: 0.367 AC XY: 27302 AN XY: 74302

Gnomad4 AFR AF: 0.215

Gnomad4 AMR AF: 0.308

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.00715

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.501

Gnomad4 OTH AF: 0.370

Alfa AF: 0.428 Hom.: 8706

Bravo AF: 0.350

Asia WGS AF: 0.154 AC: 537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.6
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs468646; hg19: chr21-42809206; COSMIC: COSV55819146; COSMIC: COSV55819146;